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After some Bio Matter Converter technology is accidentally activated, Ratchet and Clank are transported inside a Secret Agent Clank Vid-comic. The boys soon find a teleporter, and after fighting against countless Megacorp security forces, including chickenbots, security bots, security tanks and explodos. They arrive at the Communication Station, where transmissions can be sent out from the digital world and in from the analog world. They contacted Big Al for help, and he tells them of the Macro Corporeal Geo Fragmentation Ion Negator (MCGuFIN), which could transport them Back to the analog world. He says he possesses one (Previously used as a door stop) and says that he will plug it up to his copy of the Secret Agent Clank vid-comic for them to retrieve. There is a problem, however, and the MCGuFIN is split into 6 pieces, each one being put inside a different Vid-comic. After travelling between the Vid-comics and retrieving them all, Ratchet and Clank return to Al. Al informs them that they need an infolink in Maximillian's (Secret Agent Clank's Nemesis seen in the beginning of Up your Arsenal) Office. After bribing his bouncer they discover that Maximillian has already left. He has apparently used the same infolink they need to escape through to the real world, where he plans to wreak havoc. They go to confront him, he reveals that it was all a trap to try to take the MCGuFIN. They defeat him and his security cannon, and soon after this, activates the MCGuFIN by sliding down the appropriate infolink, and prepare to transport themselves back to an unknown place in the analog world.

This left an opening for the sequel, which would have been called Ratchet & Clank: Clone Home, however it was cancelled.

On their way out they can do the same things as in the preceding games. They can collect titanium bolts, upgrade weapons (to level 3), and defeat enemies. An upgrade meter for weapons is not displayed, however the HUD consists of (from left to right) an ammo meter, nanotech and bolt counter. The game is almost entirely devoid of sound except the main menu, and there are four different enemies. There is also an Arena where the duo can participate in 11 challenges. They are (in order):

Micro Alley

Cratescraper Coliseum

Lance-a-Palooza

Explodo Zone

Lance-a-Palooza 2

Timed to Die

Assassination Station

Missile Maelstrom

Assassination Station Continuation

Timed to Die Again

Boar Blitz Battle

There are 7 weapons: The Lancer, Gravity Bomb, Mini Rocket, Defragmenter, Circuit Jammer (given by Big Al) and the Boar-Zooka (obtained after completion of the Arena) and the old versatile OmniWrench

A sequel was planned in 2006, to be called Ratchet & Clank: Clone Home, but was cancelled. The plot would have been similar to Size Matters and would have had Ratchet and Clank minimizing themselves to fight some "imitators they do not find flattering". It also claimed that "Clone Home" would offer more weapons than Going Mobile, and supplied six screenshots from the game. It would also have included 15 levels.